The flu jab is associated with a reduced risk of hospitalisation in patients with heart failure, according to a trial session at Heart Failure 2016 and the 3^rd World Congress on Acute Heart Failure. The study in about 60 000 patients ends the controversy over influenza vaccination in heart failure patients and provides more robust evidence for current recommendations.

A significant proportion of hospital admissions of HF patients are thought to be triggered by influence infections. It is unclear whether flu vaccinations could reduce adverse events in patients with heart failure. Thus, more studies were needed. A benefit would confirm current recommendations by health policy makers and provide the impetus to improve uptake. If no benefit would be found, it would suggest that those guidelines that make an explicit recommendation for use in heart failure should be reconsidered.

Professor Kazem Rahimi, Deputy Director of The George Institute for Global Health, University of Oxford, UK said: “Uptake of the flu vaccination in heart failure patients is relatively low, ranging from less than 20% in low and middle income countries to 50–70% in high income countries like the UK. This may partly be because there is no strong evidence to support the recommendation in these patients. In fact, there is limited evidence to suggest that vaccination may be less effective in heart failure patients than in the general population because of their blunted immune response.”

Conduct of a randomised controlled trial would have significant practical and in some respects ethical issues. The researchers therefore used patient records for the study.

Primary care and hospital records of 4.9 million adults from the UK Department of Health’s Clinical Practice Research Datalink in 1990 to 2013 were used to assess the impact of flu vaccination on the risk of cause-specific hospitalisation in heart failure patients. A modified self-controlled case series design was applied. The risk of hospitalisation for CV disease, respiratory disease, and all causes was compared between a year in which a patient was vaccinated and an adjacent year when they were not, excluding the peri-vaccination period to minimise the risk of confounding (patients contributed more than one pair years).

The investigators identified 59 202 HF patients in the database. Flu vaccination was associated with a 30% lower risk of hospitalisation for CV diseases (HR: 0.70, 95%CI: 066-0.74), 16% lower risk of hospitalisation due to respiratory infections (HR: 0.84, 95%CI: 0.78-0.90), and 4% lower risk of all-cause hospitalisation (HR: 0.96, 95%CI: 0.95-098) in the period 31 to 300 days after vaccination, compared with the corresponding period in an adjacent vaccination-free year.

The observed associations between vaccination and hospitalisations were largest 31 to 120 days after vaccination, and in younger patients (age less than 66 years). There were no differences between men and women.

In the absence of randomised trials, this study of 59202 HF patients provides the most compelling evidence to date for the protective effect of influenza vaccination on hospital admissions.

“These findings do not suggest that influenza infection causes myocardial infarction or other cardiovascular events,” said Professor Rahimi. “A more likely explanation for the reduction in risk of cardiovascular hospitalisation is that vaccination reduces the likelihood of an infection which could in turn trigger cardiovascular deterioration. The relative effect seems to be smaller for respiratory infections, which may be due to fact that the vast majority of these hospitalisations are not related to influenza and in our study we were not able to distinguish between the different types of respiratory infection.”

Treatment was suboptimal; even in more recent years, only about half of HF patients in this setting received annual influenza vaccination. Higher uptake of annual vaccination in HF patients may help alleviate the burden of influence-related hospital admissions.

Rahimi added: “We expected a stronger relationship in younger patients since we were looking at relative risks. Older patients have multiple triggers for a cardiovascular hospitalisation so the relative impact of influenza infection could become smaller. The absolute benefit, however, is probably larger in older patients because they are at greater risk of an admission to hospital.”

The researchers validated the findings by looking at the association between vaccination and hospitalisation due to cancer, an uncorrelated outcome. As anticipated, there was no association, which supported the validity of the analysis. During the discussion the possibility was raised to look whether different results would be obtained in years in which the vaccination turned out to be a placebo vaccination, because the wrong strain of virus was used. These analyses may still be performed.

Professor Rahimi said: “Despite the measures taken, we cannot entirely rule out the possibility of residual confounding explaining at least part of the observed association. But the findings do provide further evidence that there are likely worthwhile benefits and on that basis more efforts are needed to ensure that heart failure patients receive an annual flu jab.”
Press release ESC May 23, 2016 and Late Breaking Clinical Trials Session III